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STUDY QUESTION: What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant samples in a state with >73 000 annual births? SUMMARY ANSWER: The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.3% to 15.6% of tests in the miscarriage, prenatal and postnatal cohorts, respectively. WHAT IS KNOWN ALREADY: Over the past decade, technological advances have revolutionized genomic testing at every stage of reproduction. Chromosomal microarrays (CMAs) are now the gold standard of chromosome assessment in prenatal diagnosis and pediatrics. STUDY DESIGN, SIZE, DURATION: A population-based cohort study including all chromosome analysis was performed in the Australian state of Victoria during a 24-month period from January 2015 to December 2016. All samples obtained via invasive prenatal diagnosis and postnatal samples from pregnancy tissue and infants <=12 months of age were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A research collaboration of screening and diagnostic units in the Australian state of Victoria was formed (the Perinatal Record Linkage collaboration), capturing all instances of prenatal and postnatal chromosome testing performed in the state. Victoria has over 73 000 births per annum and a median maternal age of 31.5 years. We analyzed our population-based diagnostic data set for (i) chromosome assessment of miscarriage, prenatal diagnosis and postnatal samples; (ii) testing indications and diagnostic yields for each of these cohorts; (iii) and the combined prenatal/infant prevalence of 22q11.2 deletion syndrome (DS) as a proportion of all births >=20 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANCE: During the 24-month study period, a total of 8826 chromosomal analyses were performe

Objectives: To explore the association between timing of diagnosis of common autosomal trisomies, maternal age, and socio-economic status (SES). Design(s): Retrospective study of cytogenetic diagnoses of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) in Victoria, Australia, in 2015 to 2016, stratified by timing (prenatal less than 17 weeks gestation, prenatal including or greater than or 17 weeks gestation, and postnatal before 12 months of age), maternal age, and SES region. Utilisation of prenatal testing following a live-born T21 infant was ascertained via record linkage. Result(s): Among 160 230 total births were 571 diagnoses of T21 and 246 of T18/T13. The overall and live birth prevalences of T21 were 3.56 and 0.47 per 1000 births, respectively. Compared with women from disadvantaged SES regions, women from high SES regions were more likely to have a prenatal diagnosis of a trisomy before 17 weeks than after (P <.01) and less likely to have a live-born T21 infant than a prenatal diagnosis (P <.01). There was a significant trend to higher live birth rates of T21 with lower SES (P =.004). The majority (68.5%) of women who gave birth to a live infant with T21 did not utilise prenatal testing. Conclusion(s): There is a significant relationship between lower SES, later prenatal diagnosis of trisomy, and higher live birth rate of T21 in Victoria.Copyright © 2019 John Wiley & Sons, Ltd.

STUDY QUESTION: What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant samples in a state with >73 000 annual births? SUMMARY ANSWER: The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.3% to 15.6% of tests in the miscarriage, prenatal and postnatal cohorts, respectively. WHAT IS KNOWN ALREADY: Over the past decade, technological advances have revolutionized genomic testing at every stage of reproduction. Chromosomal microarrays (CMAs) are now the gold standard of chromosome assessment in prenatal diagnosis and pediatrics. STUDY DESIGN, SIZE, DURATION: A population-based cohort study including all chromosome analysis was performed in the Australian state of Victoria during a 24-month period from January 2015 to December 2016. All samples obtained via invasive prenatal diagnosis and postnatal samples from pregnancy tissue and infants <=12 months of age were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A research collaboration of screening and diagnostic units in the Australian state of Victoria was formed (the Perinatal Record Linkage collaboration), capturing all instances of prenatal and postnatal chromosome testing performed in the state. Victoria has over 73 000 births per annum and a median maternal age of 31.5 years. We analyzed our population-based diagnostic data set for (i) chromosome assessment of miscarriage, prenatal diagnosis and postnatal samples; (ii) testing indications and diagnostic yields for each of these cohorts; (iii) and the combined prenatal/infant prevalence of 22q11.2 deletion syndrome (DS) as a proportion of all births >=20 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANCE: During the 24-month study period, a total of 8826 chromosomal analyses were performe

Objectives: To explore the association between timing of diagnosis of common autosomal trisomies, maternal age, and socio-economic status (SES). Design(s): Retrospective study of cytogenetic diagnoses of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) in Victoria, Australia, in 2015 to 2016, stratified by timing (prenatal less than 17 weeks gestation, prenatal including or greater than or 17 weeks gestation, and postnatal before 12 months of age), maternal age, and SES region. Utilisation of prenatal testing following a live-born T21 infant was ascertained via record linkage. Result(s): Among 160 230 total births were 571 diagnoses of T21 and 246 of T18/T13. The overall and live birth prevalences of T21 were 3.56 and 0.47 per 1000 births, respectively. Compared with women from disadvantaged SES regions, women from high SES regions were more likely to have a prenatal diagnosis of a trisomy before 17 weeks than after (P <.01) and less likely to have a live-born T21 infant than a prenatal diagnosis (P <.01). There was a significant trend to higher live birth rates of T21 with lower SES (P =.004). The majority (68.5%) of women who gave birth to a live infant with T21 did not utilise prenatal testing. Conclusion(s): There is a significant relationship between lower SES, later prenatal diagnosis of trisomy, and higher live birth rate of T21 in Victoria.Copyright © 2019 John Wiley & Sons, Ltd.

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHOD(S): This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULT(S): During the study period, there were 79140 births and 66166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n=61877) of women who underwent screening, and of these, 73.2% (n=45275) had CFTS alone, 20.2% (n=12486) had cfDNA alone; 5.3% (n=3268) had STSS alone, 1.3% (n=813) had both CFTS and cfDNA, and <0.1% (n=35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95%CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95%CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) a

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHOD(S): This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULT(S): During the study period, there were 79140 births and 66166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n=61877) of women who underwent screening, and of these, 73.2% (n=45275) had CFTS alone, 20.2% (n=12486) had cfDNA alone; 5.3% (n=3268) had STSS alone, 1.3% (n=813) had both CFTS and cfDNA, and <0.1% (n=35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95%CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95%CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) a